This presentation from urologist John Lindsey, MD, lays out the numerous contributing factors as well as treatments for erectile dysfunction, which affects about 30 million men in U.S. but isn’t always discussed during regular checkups. Lindsey offers help with navigating the sensitive topic, doing a complete diagnostic physical exam and running useful labs. He explains therapeutic options, including how to adjust oral meds for certain side effects, and describes investigational and experimental treatments.
All right. So uh good afternoon, everyone. Uh as, as you mentioned, we're gonna talk about erectile dysfunction today. Uh I'm John Lindsay in the Department of Urology at U CS F. Uh And I'll, I'll start with my first little soap box here. Um So Ed is tough to talk about uh tough to talk about for patients and, and also for providers. Uh I think Ed has a label can, can sometimes negatively impact self image. So that's kind of icebreakers instead of, you know, saying, you know, do you have Ed or Diagnosis of Ed? I try to ask, how is your erectile function? How are erections a little bit about me? So, uh you know, she mentioned most things in the bio there, but I did residency here at U CS F uh which I completed in June of, of last year. Uh And then I just finished the fellowship in Male Reproductive Health at Baylor uh in June of this year. Um So it's kind of three main aspects of that fellowship, uh fertility, sexual medicine and hypogonadism. And uh we'll touch on primarily sexual medicine with a little bit of the, the other two. Uh and also um a new faculty with the department just started on, on September 1st. So, uh any questions after this talk, uh please feel free to, to shoot me an email. Um and, and happy to discuss further. All right. So, uh where are we headed today? I'm gonna talk about a couple of clinical questions. Uh a little bit about the physiology and pathophysiology, uh evaluation treatment and a little bit of uh possible innovation in the field. Uh So, you know, I asked my, my roommate from med school, uh what are he's, he's an internist. Uh I asked him, what are three things you want to hear about uh in a talk on erectile dysfunction. So I use a couple of things as, as a note burner and to stimulate any questions that you, you might have uh after this talk. So, uh the first thing he, he suggested was the differences between the first line agents and that's a good place to start. So, um as of 2018, our guidelines now um are operating under this kind of shared decision making framework so that there is no true first line. Uh So if a patient presented with erectile dysfunction, any of the treatment options for erectile dysfunction uh should be available to them. Uh So whether that's oral medication or penile prosthesis, if, if uh you know the patient uh together decide on a prosthetic for, for instance, uh then that's a reasonable first choice. Um, but to that end, I will say that, um, most patients that I've seen, um, start with an oral medication before moving to some of the other, um, uh, treatment option just because it's, it's a pretty simple thing to try. Um, and then, you know, moving on with the differences between the first line agents. So here's a little schematic here and we'll talk a little bit more about it. But um you know, amongst the various agents, whether it's, you know, Cialis, Viagra or Levitra, um or Ivana, I forget the commercial name. But um they all work on uh if you can see my arrow, this PDE five and uh um enzyme uh to increase um the um cyclic GMP is little molecule here. And ultimately, that's gonna improve blood flow to the penis. So we'll talk a little bit more about that, but going back into the, the differences between the agents. So um oh, we're clicking too quickly here. Let's see. OK. So, um you know, these first three soil which is Viagra Baril, which is Levitra and then Tadalafil, which is Cialis, um they're all equally efficacious. So, um you know, choosing between efficacy is not a kind of decision point for you. They all, they all work well. Atlanta is just, it's, it's the newest one and so there's just less data on it. Uh It's kind of claimed to fame is that, you know, it can, you know, uh be ready in, in about 15 minutes, a little bit faster onset there. Um uh One thing that uh is helpful for, for patients and, and getting optimal performance from their uh PD five inhibitors Viagra and, and Levitra in particular, uh those two can be absorbed by fatty foods. Uh So I will often tell patients um taking this medication, it's um typically on a, on APR N basis so that um nothing to eat for two hours before you take that medication because it takes about two hours for the uh stomach to empty. Um And then you're gonna be taking that medication about 30 minutes to an hour before sexual activity. And that will give them the highest bioavailability of that medication. You know, you, you're not harming anything, you could take that medication right after dinner for instance, but you just may not be getting the full um full availability of the medication. Uh So that's one difference uh between the two. So do fill uh it's, it's main difference is it's very long, half life. So you can see, um you know, it's about 18 hours for the half life. Um And, and that has implications for its administration. So instead of taking it an hour before, uh which you can do, um I will often prescribe, you know, a dose of about 5 mg, you take it daily doesn't matter what time of day. Um And then it's always there in the background. So your erections are more on demand. Uh Another kind of side effect that's um mostly um you know, uh attributed to Viagra is this kind of blurry vision or blue vision. And that's because in addition to inhibiting that enzyme, that PDE five, there's cross reactivity with some of the other Phospho diocese. I think it's number six, but don't quote me on that. Um And then, you know, to a lesser degree uh Vardenafil, Levitra or Tadalafil can also have that. But uh most often see that with, with Viagra Cialis, which um you know, maybe a higher doses like the 20 mg. Um But even, even sometimes some patients with the 5 mg daily can have back pain. And so that may be a reason to uh to switch to the other ones. And I don't know whether it's clear why the back pain occurs but likely related to, to vasodilation. Um And then, you know, speaking about vasal dilation, um all of these medications uh can lead to headache, facial flushing, kind of a feeling of stuffy nose because it's dilating those blood vessels uh in the head and the blood vessels in the nose. Um So for instance, if someone's on 100 mg of, of Viagra, uh and they're having, you know, uh the headache and the facial flushing, maybe cutting that in half to 50 I might still give them, you know, um uh that response uh for, for an erection. But might reduce those, those side effects. So things to consider. Uh So another question, my, my roommate from my school uh suggested was when to refer to urology. Uh So I would say, you know, of course, after failure of oral PD five inhibitors, uh but again, with that shared decision making model, if they wanted to discuss, you know, all the available options before starting the oral, that would also be reasonable and reasonable to refer. In that instance, um any younger patients with a history of pelvic or, or perineal trauma, uh patients with significant penile deformity. So that could be an indication of hero disease. Uh And in those instances, we're looking for um curvature that's uh preventing sexual activity or um looking for plaques that we could potentially intervene on. Uh and then patients with hypogonadism. I know many primary care providers are um comfortable with testosterone therapy. But uh if not, um you know, urology is, is a place where um they can potentially receive that testosterone therapy. All right. So, moving on to anatomy and physiology, uh the penis is comprised primarily of three cylinder structures. Um you know, kind of on the, the type slide there, there's the two main chambers, uh the corporal cavernosa, um and then on the underside, uh there's the corpus fungi which surrounds the urethra and all, all three of these chambers uh will engorge during an erection. Um uh Another kind of thing that is useful for us when we're treating them is that these two top chambers um are connected. And so when you're doing therapy, like penile injection therapy with uh Trina, which I'll talk a little bit more about, you only have to inject one side uh to get that effect. The main arterial supply to the penis is this internal pendal artery. Um and then, you know, a little bit more about the, you know, physiology. So, uh you know, kind of there are many things are happening, but from a blood pro perspective, um you know, kind of three things are happening. So there's these sinusoids, these areas where blood can pool. So those are relaxed. Um you know, and, and Viagra and things like that promote that. Um and then the, the arteries also relax and improve uh promote blood flow into the penis. Then as the as the penis and gorges, it compresses on the veins on the outside uh of these carrino bodies and that compression of the veins prevents the outflow of blood. And so all those things in a concert uh lead to the erection, all right. And then you know, nerves to uh to the penis. So uh there's both um kind of autonomic as well as somatic innovation uh to the penis. Um And uh you can see here these nerves are right behind this purple structure, which is the prostate. Uh these nerves are, you know, and, and a normally functioned person um providing you know, input to the penis and, and promoting erection. Um and kind of an aside here. So for patients who have their prostate removed and provide their cancer isn't, is, isn't very advanced. Um Surgeons will try to preserve these, these nerves are running behind the prostate uh to preserve erectile function. Uh And uh sometimes the tissue that this is running is referred to as the, the veil of Aphrodite. So, um we, we work hard to try to preserve that. Uh and then kind of coming back to the physiology. So, uh again, uh Viagra Cialis, they're all working here on this enzyme PDE five. And that's increasing or uh maintaining the production of um this cyclic GMP ultimately uh to relax with muscles. So it's decreasing, calcium, et cetera. Uh The other thing that I can kind of see here. So those nerves running in that, that vein of Aphrodite uh and someone who's, who's functioning, um normally they release nitric oxide uh which stimulates this protein here um to, to do the same thing to increase the quantity of the cyclic GMP. Uh So that's, that's more than the most one I know. But now you have some more sort of history there. All right. So, moving on to the pathophysiology of erectile dysfunction. Uh But first we'll do a little bit of art. Uh So my nooky days are over, my pilot light is out. What used to be my sex appeal is now my water felt time was when on its own accord. For my trousers, it would spring. But now I've got a full time job to find the gosh, darn thing. It used to be embarrassing the way it would behave for every single morning it would stand and watch me shave. Now, as old age approaches it triggers me the blues to see it hang its little head and watch me tie my shoes. All right. So, back to work here. So Ed defined uh the inability to attain or maintain sufficient penile rigidity for sexual satisfaction. Um It's estimated that as many as 30 million men in the US are affected by this. Um And, you know, there's some studies that can show that by, by age 40 as, as much as 50% of men have some degree of erectile dysfunction, whether that's uh a reduction of rigidity, difficulty attaining or difficulty maintaining that erection. So I try to use those numbers to, to reassure men. Uh So they feel, you know, kind of less. Um like it's, you know, something they've done wrong sym pathology on their end. Um All right. And so many things can, can lead to Ed, uh probably most commonly vascular genic. And we talked a little bit and we'll talk more about those things neurogenic. So, anything that's gonna take out those nerves, um particularly uh those carousal nerves are behind the prostate, um an atomic causes. So, uh in diabetes. For instance, we see a lot of calcification, bio tissue hardening of tissues. And so those smooth muscles that need to relax and pull blood into the penis can't relax as well. Um In some of those disease states, there are medications also that can contribute to this and then psychogenic is a, is its own class of, of, of contributions. And so we'll talk about more, more about all those things. Um So, you know, looking at kind of the anomic and vascular genic contributions. I I tell patients that um diabetes, hypertension, you know, hyperlipidemia, smoking, all these things contribute to thickening and hardening of arteries, uh which results in more narrow lumens and reduced blood flow to the penis. Um that reduced blood flow is also creates a more uh ischemic environment for the nerves um that, that need to release the nitric oxide to promote the erection. So you kind of get this 12 punch uh when the vascular health is is not good. Um I try to use that to encourage patients to, to uh modify their lifestyle or that's exercise, um weight reduction, et cetera, uh cessation of smoking. Um I also uh always try to check a serum testosterone and it also recommended by guidelines uh on a new patient presenting with erectile dysfunction. Uh So for many men, uh correcting low testosterone can be adequate to restore erectile function. Uh low libido is the most common sexual symptom of low T. Uh So asking about sexual desire during the history, can clue you in to the likelihood of low testosterone. Um Also of note, uh low testosterone can be associated with development of other co so insulin resistant type two diabetes, um increase the deposition of abdominal fat. So um a lot, lot going into to testosterone deficiency. Um uh another nice thing. So ed has been promoted by many experts as an early indicator of systemic endothelial dysfunction, uh an indication for cardiac risk stratification. So, um you know, some studies show that um erectile dysfunction can kind of be the canary in the coal mine for the development of cardiovascular disease. Um and then, you know, on the primary side as providers, you know, you can kind of use that as a motivating factor. So for, for patients who perhaps aren't uh taking the cardiovascular health seriously or you know, the impact that is having on other end organs, the kidneys, the eyes, um sometimes, you know, letting them know the impact this is having on erectile function can be, can be uh motivating enough for them uh to, to make those lifestyle modifications. Uh So we talked about medications that can contribute. Uh you guys know most uh most of these classes. So, diuretics and beta blockers are, are, are big ones. But other things to consider, you know, these um you know, opioids, uh whether, you know, taking kind of uh period operatively uh for surgery can even that acute period can be enough to suppress testosterone can cause transient dysfunction. Certainly, those on chronic opioids will uh suppression of testosterone production, which can lead to erectile dysfunction. Uh tobacco just because of the effects of smoking on uh vasculature. Um alcohol, uh it's kind of a mixed one. So a small small dose of alcohol can sometimes be helpful just because it's reducing anxiety. But uh higher doses of alcohol um are, are, are definitely um uh not helpful for erectile function. And then marijuana as well, studies are showing that chronic use of marijuana um reduces testosterone production and that, you know, will contribute to erectile dysfunction. So all things to uh discuss with patients. Uh So psychogenic ed, uh there are many, many ways that psychosocial factors can contribute to erectile dysfunction, um placebo effects reliably and in many trials of ed um uh are, are seen. So that implies that even even in cases where, you know, there's an organic cause for diabetes or um uh neurogenic cause, uh there's still unmet social needs, psychosocial needs. So, uh we will, we try our best to refer these patients to uh to sex therapist. I'll talk a little bit more about that. So uh moving on to diagnostic evaluation uh in fellowship, I started giving all men this form here. So this is the uh sexual health inventory for men. We call it the Shin. Uh It's a nice icebreaker uh to discuss erectile function. Many men will not have even planned to discuss erectile dysfunction in their, their visit with urology uh but are happy for the for the reminder. So, um it also kind of provides me with this uh structure delineation of the the degree of erectile dysfunction uh which is helpful in deciding the next steps. Um And then uh in the sexual history, the goal there is just to assess psychogenic, um you know, you know, for instance, the relationship stressors or organic causes. So you have those things that we mentioned hypertension, hyperlipidemia, diabetes or, or whether both directly uh in the medical history, you guys, you know, you kind of know the main ones that are contributory. And then again, you know, opioids, alcohol and marijuana users can also be um kind of ones that you don't think about immediately uh as contributors to erectile dysfunction um because they're going through the hormonal pathway and contributing to erectile dysfunction and then COVID, uh you know, it's kind of a question mark. So, uh during my fellowship, uh we saw cases of men who um had a reduction in spermatogenesis, reduction, reduct, um sorry, reduction in sperm production, uh reduction in uh testosterone and and erectile dysfunction, dysfunction, kind of lining up with uh an acute COVID infection and you know, it's transient. Uh but uh something that we'll have to, to study more uh to understand the impact that COVID has had on these things. Um and then going, you know, coming back to the psychosocial history, um we're looking for uh things like a diagnosis of a mood disorder. Uh being managed with Ssris paroxetine is kind of one of the nefarious ones for erectile dysfunction, anxiolytics looking for new emotional stressors, whether that's with work or in a relationship. Um and uh you know, kind of moving on to the physical exam. Uh so things that we're looking at, so the body habit is so fat cells will convert testosterone into estrogen naturally. And so, for people with increased adiposity, they're having increased production of estradiol which feeds back uh to the brain and inhibits production of testosterone. So, uh weight loss can, can be helpful in that end you cardiovascular, you're looking for hypertension, other things that contribute to poor poor vasculature, uh neurologic again, um you know, sometimes you see patients with paraesthesia, uh high A one C uh type two diabetes and um that kind of clues you into to what's contributed to the recile dysfunction there. And then on the genital exam, um you know, uh you're looking for um penile plaques or curvature uh that may suggest spr disease. In that case, you want to refer to urology if the patient is interested in further evaluation um atrophic testicles. So decrease in testicular size that could suggest hypogonadism uh and and prompt measuring of uh the serum testosterone. So, um you know, typical labs to get in evaluating uh erectile dysfunction, just A B MP CBC A one C li profile um and also an AM testosterone. So, um testosterone peaks uh in the morning. And so that's what, that's what we use as our barometer, that am testosterone to determine uh the normal level which you know, can be anywhere between 300 1000 nanograms per deciliter. Um All right, we have here. OK. And then, you know, on our end, an addition, additional diagnostic evaluation that we would do uh perhaps as someone who's uh failed oral therapy or uh give that younger patient who may have, have had uh hell or perineal trauma um as a penile Doppler uh to assess that, that inflow as well as the outflow. So, you know, to form an erection, you gotta have good inflow of blood and you can't have too much of the blood leading. So that's what we look for. Uh we do an injection before the start of the procedure to generate an erection. And in addition to looking at the dynamics of the blood flow, we're looking for a penile plaque, looking for curvature, um uh that might suggest Perrone disease. All right. Um And then, you know, sort sort of uh treatment. Um I can hear many of my attending saying anything that's good for the heart is good for the penis. Um It's an easy way for patients to think about preserving erectile function through diet exercise and uh modification of recreational activities, uh tobacco, marijuana. Um Additionally, uh I'm a cyclist and the Bay area has many cyclists. So, if, if you have any of these patients, I recommend that they use a saddle with uh depression in the middle of the seat uh to reduce pressure on uh the erectile tissue in the perineum. Uh but you know, it's a small side. Uh So for psychosexual psychosexual therapy or possible uh modified diaz sides. Um beta blockers and Ssris uh for men being treated for ed. Um with American Urological Association recommends that we refer to a mental health professional uh to improve communication between partners um to improve treatment, adherence, reduce anxiety uh and arrive at treatments that work for both partners. All right. Uh and the testosterone therapy. So, uh there are many, many forms of testosterone therapy. Um and, and this alone can be enough to resolve erectile dysfunction in some men. Um And you know, in fellowship, I'd say, you know, the most common one that, that I saw was kind of intramuscular but um implanted pillows also work well for patients and also topical and oral formulations. Uh important considerations before starting uh fertility uh before starting testosterone therapy and fertility planning. So, if anyone uh is planning fertility, we would not want to start them on testosterone therapy because that's gonna reduce your ability to make sperm. Um One with significant cardiovascular disease. I want to have a discussion more with their um, cardiologist, there's no strong evidence in either direction, whether it's helpful or harmful to social therapy. But, um, for someone with complex cardiovascular history, you want to have a discussion with the patient and the cardiologist before starting therapy, uh, making sure that you're assessing the liver function. Um, yeah, warning patients about a potential test, testicular atrophy. Uh, so how many patients, um, you know, plugged in with, um, testosterone clinics, um, uh, can have uh testicular atrophy if, if they're solely on testosterone. Um and then, you know, frequently checking hematocrits. Uh So, you know, roughly every, every six months, you wanna make sure that um hematocrit is not above 54% per per guidance. All right. And so this, this area you guys are uh I assume very familiar with um you know, one regimen that um I, I liked and that I saw in fellowship was starting patients on um you know, roughly 5 mg of Cialis daily. Uh And again, you know, kind of going back to the earlier discussion. Cialis doesn't matter what time of day you're taking it. Um And uh you know, it's, it's just kind of there in the background. Uh So for a new start for that patient, I, you know, I let them know that it can take about because the half life is 18 hours, you know, technically takes 3 to 4 days for it to build up. But I just tell him, you know, give it a week before you decide how well that's working for you. Um And then depending on the response that they're getting with that, that five daily you can on top of that still add, um Viagra Sildenafil. So 100 mg as needed. And again, uh has to be an empty stomach. So two hours after eating 30 to 60 minutes before sexual activity, um, so you can do these things in combination or you do either or uh but those are my kind of go tos um you know, important things to ask about the cardiovascular history. Uh So anyone, you know, on some link with nitrogen, for instance, as absolute contraindication. Um And then also if I have a patient who's, for instance, on Flomax, I'm just separating the timing of the two. So if they're taking Flomax at night, uh start a new start for tada. So we have it taken in a and just so you don't have the uh potential uh hypertension from the two. And then another important thing to, to remind patients uh if they have an irrational lasting four hours, that's emergency, that should come to uh the emergency department for uh further evaluation. Um I will say that it's um it's rare from, from just an oral um PD five to have this uh prior but um it's something that all patients should be, be aware of. Uh another option for treatment of ed. Um And the primary care setting uh is a vacuum erection device. So um it's relatively low cost, it's a conservative option. Um Important things to know that the V should have a vacuum limiter uh to reduce penile injury. And patients should also be counseled not to wear uh the constriction. So you, you know, you use the, the pump to pull blood into the penis to generate erection. And then these rings that you can see here you put on, uh get to the base of the penis and uh hold that blood in place uh for sexual activity, but they shouldn't keep that on for more than 30 minutes. All right. Uh Other treatment options. Um uh kind of on the urology side, we talked about this intracavernosal injection. So, uh we take a tiny, you know, when patients hear about this. Uh and, and they have not heard about it before. They're normally very alarmed. Uh uh but we took a very tiny needle, you know, something on the, on the order of 28 gauge, 29 gauge. Um And uh this picture is not quite accurate. You want to go like the three o'clock or nine o'clock position. Uh But uh most common formulation is trimix. So three medications that are all promoting basal dilation, Pentamine, pat of all pro um and you know, the another formulation of just bii so just two of these, these medications, but it works very well. So, uh for patients who are, um, you know, starting to fill PD five inhibitors or, you know, recently just kind of failing PD five inhibitors. This is, this is a great next step for them, um, and have a, um, a pretty good response. Um, the tricky thing with, uh, starting that is just making sure you're not, uh, overshoot, uh, the appropriate dose for them, uh, because that can certainly lead to prey more so than the oral medications. And, um, so finding out that balance, uh, can, can become challenging and then a, a much frequently used, um, alternative to the, the injection is, um, used. So you're, um, doing entry eal suppository of, uh, I think it's just pros but don't quote me on that. Um, but, uh, it's, it burns for most patients. Uh, it's, it creates burning sensation in the urethra. So, um, I, I think maybe in my training, I saw one patient, uh, uh, that was using this, um, and, and, and happy with it. Uh, all right. So other treatment options, um, is the, uh, penile prosthesis. Um, and, uh, it is obviously, you know, something that, that reconstructive urologists do as well as, um, you know, urologists who are trained in my special no reproductive health. Um, so the, the main components, uh, of this, you know, we have a reservoir, um, which I'll, I'll show you kind of the layout of the body, the pump, uh, and the cylinders. Um, so the, uh, the pump, you know, sits here in the scrotum. Uh patients kind of squeeze on this end of it to inflate the penis. So water will move from uh the reservoir into the cylinders to generate an erection. There's a little button that's not, not well visualized in this image that they press to um uh to, you know, promote D two me, you know, and um to pro the water going back into the reservoir. So, um you know, patients who are at this stage where oral medications aren't working anymore or IC I is either something that they don't want to try or it no longer works. Uh This is a great option for them. Um And both, both the patients and their partners are, are very happy with this sensation in the penis, uh remains intact. Patients remain the, retain the ability to, to orgasm. Uh So it's something they're very happy with you. There are some limitations, the uh it's a mechanical device. So, you know, the, the general life for it is, you know, in the order of 8 to 10 years. Uh so things that could fail or, you know, there could be a leak somewhere or um you know, some, you know, once some of the tubing kind of falls apart, we also leaking. So uh they, they do have to be um they're, they're not a one and done and then, you know, other risks, you know, sometimes um infection can develop when we take a lot of measures to prevent infection, but it is a foreign, foreign body and, and implanted. So, infection risk is nonzero. Uh so that could be another reason for explant. But overall patients are, are very happy with these um kind of uh upcoming treatments. I don't know if that's the right word, but uh shockwave therapy is something that um we did in my fellowship and it's still kind of investigational status. But um our, our protocol was twice weekly, you know, for um you know, roughly 5 to 10 minutes, uh we administer these low intensity shock wave. And the, and the thought behind that is uh it's creating a, you know, kind of a micro level of injury that's uh stimulating uh vascular genesis um and, and perhaps nerves as well um and restoring some erectile function. And so the ideal patients for, for this are, are men who um are on oral PD five inhibitors or maybe just starting to kind of fill on oral PD five inhibitors and this can give them a boost. And uh I think, you know what I've seen in clinic, you know, somewhere between maybe 40 60% of men do notice uh an improvement in retile function after this therapy. Uh Another one that's kind of uh popping up everywhere is um APR P platelet rich plasma. Uh and even, you know, kind of a lesser grade right now, it's in the experimental stage. So no clear evidence that it's helpful um and improving erectile function. But uh there are many, many clinics, um not necessarily urology clinics, but just kind of um you know, general clinics who are doing pr P for for many indications um are are trying to solve erectile function. So um just need more data to, to know how well um that, that will work for patients.